The objectives of this project are to obtain an increased understanding of hepatitis E virus (HEV) and related viruses with the goal of designing strategies for their control. Although sequence analysis of HEV clones is still rather limited, preliminary data indicate that this virus, like most single-stranded RNA-containing viruses, exhibits significant heterogeneity of genomic sequence. This has potential implications for vaccine development, since heterogeneity of the degree exhibited by this virus is sometimes associated with serotypic variation. However, the limited data available on cross-challenges in primate models suggest that even relatively divergent strains will elicit cross-protective antibodies. 1. A full-length cDNA clone of the Sar-55 strain of HEV has been constructed and is being tested for infectivity. 2. The major HEV structural protein has been obtained by expression of part of the Sar-55 genome in insect cells using a baculovirus expression vector. 3. An ELISA for anti-HEV IgG and IgM has been developed. 4. Prolonged infection of a small percentage of Vero cells in culture has been documented using the polymerase chain reaction.